1. Field of the Invention
The present invention relates to a fluid handling system, apparatus and method. It is particularly useful for mixing liquid samples with previously separated processing liquids, such as reagents or diluents, in continuous flow analyzers.
2. Brief Description of the Prior Art
Automated apparatus for the analysis of liquid samples as a flowing stream was disclosed by Skeggs in U.S. Pat. Nos. 2,797,149 and 2,879,141, both assigned to the instant assignee. In this basic apparatus, the liquid samples are sequentially aspirated from storage containers into a conduit, each sample being separated from the next sample by succesive segments of air. Air is introduced between successive segments of an individual sample to promote intrasample mixing and between samples to prevent intersample contamination. Such air/sample sequences can be alternated with air/wash liquid sequences to further insure against carryover. As illustrated by Ferrari in U.S. Pat. No. 2,933,293, also assigned to the instant assignee, a junction in the conduit continually introduces a processing liquid, such as a reagent, into the alternating sequence of air and sample segments and, also, into wash segments when present. In apparatus such as that described above, the fluid stream containing air segments and segments of combined sample and processing fluid can be "debubbled" immediately before entering a flow cell through which the reacted samples are read. Thus, the successive sample segments contact one another just before entry into the flow cell. The debubbler was positioned adjacent to the flow cell to prevent undesirable intermixing between liquid segments. Alternatively, as in high throughput systems, the air segments can be passed through the flow cell.
Ferrari et al, U.S. Pat. No. 3,109,713, assigned to the instant assignee, also discloses an analysis apparatus in which procesing fluids, such as reagents, are continuously introduced into a stream of alternating air and sample segments as shown in the juncture of conduits 42 and 44 in FIG. 1. A series of substantially identical segments of a single processed sample are passed through a debubbler. The air is abstracted to consolidate and blend the segments of processed liquid which are passed through a flow cell. Debubbling and blending was done to prevent disruption of colorimeter operation by the optical properties of the air bubbles.
Smythe et al, U.S. Pat. No. 3,479,141, likewise assigned to the instant assignee, discloses a transport system for automatic analysis apparatus in which a series of aqueous liquid samples are processed as a flowing fluid stream with substantially no contamination between segments. A fluoropolymer conduit and intersample carrier segments of silicone are used. The silicone, in effect, encapsulates the aqueous liquid segments during passage along the conduit. Thus, contamination between successive liquid segments is substantially completetly eliminated. Further, in such improved apparatus, it has been recognized that debubbling defeats the principal advantages of this approact.
Smythe et al, U.S. Pat. No. 3,804,593, also assigned to the instant assignee, discloses an analysis apparatus having a first tube which receives samples from vessels on a turntable and a second tube which receives reagent liquid from a stationary reagent container. Both tubes are concurrently inserted into their respective containers repeatedly to provide a flowing stream of segments of liquid sample interspersed by air segments and a similarly segmented stream of reagent. These streams are merged to form an alternating sequence of air and sample/reagent segments which are then analyzed. As in the other patents discussed, each of the samples is reacted on-line with only a single reagent, the reaction beginning immediately upon the reagent being introduced into the system. No capability for testing samples with only selected reagents is provided. Since many samples are run for only one or a few particular analyses, this is wasteful of time and reagents and thus, more costly to the patient.
In each of the prior art systems, the reagent is reactive with the sample immediately upon introduction into the system. Accordingly, such systems are not suitable for performing two-stage reactions, i.e., those in which a first reaction must be completed before a second reaction is commenced. Such reactions would require that the reagents be introduced at different points or locations along the system. This would require complication of the conduit system and, also, present severe phasing problems, particularly when the system is adapted to perform different analyses, on a random basis, along a same conduit. Such phasing problems would be especially severe in high flow rate systems using small volumes of sample. For these reasons, prior art systems have generally been adapted only to perform single-stage reactions.